Temperature and pressure limits of guanosine monophosphate self-assemblies

Abstract

Guanosine monophosphate, among the nucleotides, has the unique property to self-associate and form nanoscale cylinders consisting of hydrogen-bonded G-quartet disks, which are stacked on top of one another. Such self-assemblies describe not only the basic structural motif of G-quadruplexes formed by, e.g., telomeric DNA sequences, but are also interesting targets for supramolecular chemistry and nanotechnology. The G-quartet stacks serve as an excellent model to understand the fundamentals of their molecular self-association and to unveil their application spectrum. However, the thermodynamic stability of such self-assemblies over an extended temperature and pressure range is largely unexplored. Here, we report a combined FTIR and NMR study on the temperature and pressure stability of G-quartet stacks formed by disodium guanosine 5′-monophosphate (Na25′-GMP). We found that under abyssal conditions, where temperatures as low as 5 °C and pressures up to 1 kbar are reached, the self-association of Na25′-GMP is most favoured. Beyond those conditions, the G-quartet stacks dissociate laterally into monomer stacks without significantly changing the longitudinal dimension. Among the tested alkali cations, K+ is the most efficient one to elevate the temperature as well as the pressure limits of GMP self-assembly.

K+ vs. Na+ Effects on the Self-Assembly of Guanosine 5′-Monophosphate: A Solution SAXS Structural Study

“…Indeed, it has been demonstrated that this band is sensitive to the guanine structuring, since it moves from about 1693 cm −1 , found in DNA quadruplex, to 1655-1670 cm −1 , observed for single stranded DNA [35,36]. Similar results were also observed in the case of GMPNa 2 at basic pH: the self-association in quadruplexes was observed to determine a blue shift from 1657 cm −1 to 1675 cm −1 [37]. Therefore, the temperature dependence of the frequency of the C 6 =O 6 stretching modes could be a good indication for the assembling/disassembling of GMP in solution.…”

Applications of guanine quartets in nanotechnology and chemical biology

“…This includes other Xraybased techniques (for example, smallangle Xray scattering (SAXS)) 42 , along with various microscopy techniques: atomic force microscopy (AFM) was applied to charac terize the selforganization of GMP on mica 43 , SEM was applied to investigate the folding parameters and global topology of micrometrelong Na 2 (5′GMP) assemblies 36 and scanning tunnelling microscopy (STM) was applied in combination with density functional theory (DFT) calculations to assess whether and how Gquartets can be assembled on surfaces (either Au(iii) 24,44 or highly ori ented pyrolytic graphite (HOPG) 45 surface) in solventless conditions, with simple or sophisticated guanine deriva tives, in the absence or presence of Na + , K + or Ca 2+ cations. Spectroscopic techniques provided invaluable clues about Gbased selfassemblies in solution; these include Fourier transform infrared (FTIR) 46 , infrared multiple photon dissociation (IRMPD) [47][48][49] and RAMAN 50 spectroscopies, along with electronic and vibrational circular dichroism for instance (ECD 51 and VCD 52 , respectively) combined with degenerate coupled oscillator (DCO) calculations 52 and NMR 53,54 , notably diffusionordered spectroscopy (DOSY) NMR, which were successfully implemented to characterize the cationtemplated GMP aggregation in nearphysiological conditions. Finally, theoretical mod els were provided via molecular dynamics (MD) 55,56 and molecular mechanics (MM) 57 , notably for both describ ing cationtemplated Gquartet formation and simulating in silico the movement (channelling) of cation (e.g.…”

Advanced Raman Spectroscopy Detection of Oxidative Damage in Nucleic Acid Bases: Probing Chemical Changes and Intermolecular Interactions in Guanosine at Ultralow Concentration

“…In the past, the characterization of the self-assembled structures has been carried out exploiting nuclear magnetic resonance spectroscopy, scanning electron microscopy, dynamic light scattering, and fingerprint Raman analysis. 61 , 69 − 71 To the best of our knowledge, the low-frequency G-tetrad Raman response has not been reported yet and has the advantage of containing intense and easily monitored markers of tetrad formation.…”

“…Indeed, the different structure and electronic distribution in oxidized nucleotides produce structural rearrangements at the intermolecular level, modifying the extent and the properties of long-range intermolecular interactions, which are reflected in the terahertz Raman response. In the past years, the characterization of the self-assembled structures has been carried out exploiting nuclear magnetic resonance spectroscopy, scanning electron microscopy, dynamic light scattering, and Raman in the fingerprint region [63,[71][72][73]. To the best of our knowledge, the low frequency Raman response of intermolecular G structures has not been reported yet and has the advantage of containing intense and easily monitored spectral markers of tetrads formation.…”